Clinical Pearls · 2026

Efficacy Outcomes After 5 and 52 Weeks of Xanomeline-Trospium in Inpatients and Outpatients

The question:How should the 5-week and 52-week PANSS results be read when the two trials enrolled different populations?

The Two Cohorts Side by Side

Xanomeline-trospium arm unless placebo is shown

Pooled EMERGENT-1, -2 and -3n=6405-Week

EMERGENT-5n=55852-Week

Who enrolled

Design

Randomized, placebo-controlled; inpatients

Open-label, single-arm; stable outpatients at US sites

Entry criteria

PANSS total 80 to 120; CGI-S ≥4

PANSS total ≤80; CGI-S ≤4

Baseline

97.5PANSS total5.1CGI-S

66.0PANSS total3.4CGI-S

Discontinued

27.6%

51.1%

Symptom change

PANSS total

−19.4vs −9.6 with placebo at week 5Difference −9.9, 95% CI −12.4 to −7.3; Cohen d 0.65

−5.5at week 52No comparator arm

CGI-S

−1.1vs −0.5 with placebo; difference −0.6

−0.4at week 52

Improvement first seen

At the first PANSS check, 2 weeks into treatment

At the first PANSS check, 1 week into treatment

PANSS = Positive and Negative Syndrome Scale; CGI-S = Clinical Global Impression–Severity.

Responders

≥30% PANSS reduction, same threshold in both

5-Week≥30% improvement at week 5

41.4%

20.9%

Xanomeline-trospium130/314

Placebo68/326

Difference 20.5 points

52-Week≥30% improvement, by visit

7.2%

12.1%

15.0%

17.7%

22.7%

27.4%

26.3%

27.5%

29.3%

31.4%

30.0%

Wk 1n=530

Wk 4n=480

Wk 8n=432

Wk 12n=395

Wk 16n=374

Wk 20n=350

Wk 24n=334

Wk 32n=313

Wk 40n=297

Wk 48n=287

Wk 52n=283

52-week values describe the participants still assessed at each visit.

5-Week

Take-home: short-term improvement was seen over 5 weeks in an acutely ill inpatient population

52-Week

Take-home: long-term improvement was seen over 52 weeks in a less severe outpatient population

Safety

Selected events only, not the full safety profile; details in the companion safety pearl

Safety

67.9% had an adverse event vs 51.3% with placebo; 5.9% vs 4.4% stopped for one

82.3% had an adverse event; 17.7% stopped for one

Pearl

Improvement was seen in both cohorts, though the rate and magnitude of improvement differed between them. The 5-week trials enrolled patients in acute exacerbation, while EMERGENT-5 followed stable patients for 52 weeks. The results are not directly comparable given differences in duration, design, and patient status.

Based on

Kaul I, Sawchak S, Claxton A, et al. Schizophrenia. 2024;10:102.

Kaul I, Claxton A, Sawchak S, et al. J Clin Psychiatry. 2025;86(1):24m15497.

Kaul I, Claxton A, Chaturvedi S, et al. Schizophr Res. 2026;288:86–94.

Sponsor

Financial support was provided by Bristol Myers Squibb. Psychiatrist.com independently developed the content and maintained final editorial control. The trial authors include employees and consultants of the manufacturer; their disclosures appear in the full publications. The approved labeling does not address 52-week outcomes. This summary does not replace prescribing information.